Spreadsheet Research Articles

Interfacial Organization and Forces Arising from Epithelial-Cancerous Monolayer Interactions.

The interfacial interactions between epithelia and cancer cells have profound relevance for tumor development and metastasis. Through monolayer confrontation of MCF10A (nontumorigenic human breast epithelial cells) and MDA-MB-231 (human epithelial breast cancer cells) cells, we investigate the epithelial-cancerous interfacial interactions at the tissue level. We show that the monolayer interaction leads to competitive interfacial morphodynamics and drives an intricate spatial organization of MCF10A cells into multicellular finger-like structures, which further branch into multiple subfinger-like structures. These hierarchical interfacial structures penetrate the cancer monolayer and can spontaneously segregate or even envelop cancer cell clusters, consistent with our theoretical prediction. By tracking the substrate displacements via embedded fluorescent nanobeads and implementing nanomechanical modeling that combines atomic force microscopy and finite element simulations, we computed mechanical force patterns, including traction forces and monolayer stresses, caused by the monolayer interaction. It is found that the heterogeneous mechanical forces accumulated in the monolayers are able to squeeze cancer cells, leading to three-dimensional interfacial bulges or cell extrusion, initiating the p53 apoptosis signaling pathways of cancer cells. We reveal that intercellular E-cadherin and P-cadherin of epithelial cells differentially regulate the interfacial organization including migration speed, directionality, spatial correlation, F-actin alignment, and subcellular protrusions of MCF10A cells; whereas E-cadherin governs interfacial geometry that is relevant to force localization and cancer cell extrusion, P-cadherin maintains interfacial integrity that enables long-range force transmission. Our findings suggest that the collaborative molecular and mechanical behaviors are crucial for preventing epithelial tissues from undergoing tumor invasion.

Mentorship Programme for Undergraduate Medical Students.

Mentorship is seen as a continuous journey of discovery, shared learning, and personal and professional development to achieve leadership and excellence. Medical schools can be monitored with respect to the provision of mentorships as a quality characteristic. So, the aim of our study was to know the prevalence and the impact of mentorship program in medical schools of Nepal and the need of this program in medical schools all over Nepal. A descriptive cross-sectional study was conducted among medical students in medical schools in Nepal. Ethical approval from the Nepal Health Research Council (NHRC) was obtained (Ref. 667). The cumulative data obtained nationwide was entered in computerized spreadsheet software (Microsoft Excel) and analyzed using MS Excel and SPSS 16.0. Patan Academy of Health Sciences (PAHS) 131 (50.8%) had highest prevalence of mentorship program. Out of 258 students, 110 (42.6%) knew that there was mentorship program in their medical schools. The study found the role of mentors in building rapport with faculties (61.82%), developing professional skills (81.82%) and learning evidence-based medicine (74.55%). 98.8% participants soughed for the need of this program in their medical schools. The prevalence of mentorship program among medical school in Nepal was found to be low. Individuals involved in the mentor-mentee relationship found the role of mentor not only on academics but also on their personal and social enterprises. Medical students who were familiar with the concept of this program reported its need in medical school.

Preliminary cost forecasting and optimization for the construction of steel pedestrian bridges in Egypt

PurposeThis research aims to create a methodology that integrates optimization techniques into preliminary cost estimates and predicts the impacts of design alternatives of steel pedestrian bridges (SPBs). The cost estimation process uses two main parameters, but the main goal is to create a cost estimation model.Design/methodology/approachThis study explores a flexible model design that uses computing capabilities for decision-making. Using cost optimization techniques, the model can select an optimal pedestrian bridge system based on multiple criteria that may change independently. This research focuses on four types of SPB systems prevalent in Egypt and worldwide. The study also suggests developing a computerized cost and weight optimization model that enables decision-makers to select the optimal system for SPBs in keeping up with the criteria established for that system.FindingsIn this paper, the authors developed an optimization model for cost estimates of SPBs. The model considers two main parameters: weight and cost. The main contribution of this study based on a parametric study is to propose an approach that enables structural engineers and designers to select the optimum system for SPBs.Practical implicationsThe implications of this research from a practical perspective are that the study outlines a feasible approach to develop a computerized model that utilizes the capabilities of computing for quick cost optimization that enables decision-makers to select the optimal system for four common SPBs based on multiple criteria that may change independently and in concert with cost optimization during the preliminary design stage.Social implicationsThe model can choose an optimal system for SPBs based on multiple criteria that may change independently and in concert with cost optimization. The resulting optimization model can forecast the optimum cost of the SPBs for different structural spans and road spans based on local unit costs of materials cost of steel structures, fabrication, erection and painting works.Originality/valueThe authors developed a computerized model that uses spreadsheet software's capabilities for cost optimization, enabling decision-makers to select the optimal system for SPBs meeting the criteria established for such a system. Based on structural characteristics and material unit costs, this study shows that using the optimization model for estimating the total direct cost of SPB systems, the project cost can be accurately predicted based on the conceptual design status, and positive prediction outcomes are achieved.

Maximum Likelihood Instead of Least Squares in Fracture Analysis by Means of a Simple Excel Sheet with VBA Macro

This technical note illustrates a linear regression algorithm based on the Maximum Likelihood Estimation (MLE), with a related Excel spreadsheet and VBA program, adapted to the case of fracture aperture data sets in which sampling of the smallest values is problematic. The method has been tested by means of Monte Carlo simulations and exhibits significantly better convergence against Least Squares criterion (LSM). As the method is conceptually simple and, following the indications illustrated here, the relative spreadsheet can be easily designed, it may be routinely used, instead of the Least Squares, in fracture analysis. Furthermore, the proposed method, with the appropriate modifications, might be potentially extended to other cases in geology and geophysics, in which significant biases at the lower limits of the sampling scale occur.

Insight into the Dependence of Photovoltaic Performance on Interfacial Energy Alignment in Solar Cells with Mobile Ions

A key aspect in the optimization of perovskite (PVK) solar cells is the mitigation of interface losses, which are determined by energy band offsets and recombination. Counterintuitively, recent experimental evidence on inorganic PVK solar cells shows that increasing band offsets may improve open‐circuit voltage at efficiency levels over 20%. In order to improve the knowledge of the impact of interfaces, the authors model solar cells consisting of an intrinsic absorber material containing mobile ions, sandwiched between two wide‐gap charge transport layers. The results show that minimizing band offsets decreases interface losses in various scenarios, but cannot be adopted as a universal optimization rule. For instance, even in the absence of interface recombination, unequal majority carrier band offsets avoid high injection conditions. Moreover, assuming a fixed band offset at one interface, the band offset at the opposite interface should be reduced if it shows the highest interface recombination, or increased if it shows the lowest recombination. Remarkably, it is found that solar cells with mobile ions hold the potential to outperform of ion‐free counterparts, depending on the extent to which the interplay between band offsets and Debye layers result in the establishment of a majority carrier concentration in the intrinsic absorber.

Melt electrowritten scaffold architectures to mimic tissue mechanics and guide neo-tissue orientation

All human tissues present with unique mechanical properties critical to their function. This is achieved in part through the specific architecture of the extracellular matrix (ECM) fibres within each tissue. An example of this is seen in the walls of the vasculature where each layer presents with a unique ECM orientation critical to its functions. Current adopted vascular grafts to bypass a stenosed/damaged vessel fail to recapitulate this unique mechanical behaviour, particularly in the case of small diameter vessels (<6 mm), leading to failure. Therefore, in this study, melt-electrowriting (MEW) was adopted to produce a range of fibrous scaffolds to mimic the extracellular matrix (ECM) architecture of the tunica media of the vasculature, in an attempt to match the mechanical and biological behaviour of the native porcine tissue. Initially, the range of collagen architectures within the native vessel was determined, and subsequently replicated using MEW (winding angles (WA) 45°, 26.5°, 18.4°, 11.3°). These scaffolds recapitulated the anisotropic, non-linear mechanical behaviour of native carotid blood vessels. Moreover, these grafts facilitated human mesenchymal stem cell (hMSC) infiltration, differentiation, and ECM deposition that was independent of WA. The bioinspired MEW fibre architecture promoted cell alignment and preferential neo-tissue orientation in a manner similar to that seen in native tissue, particularly for WA 18.4° and 11.3°, which is a mandatory requirement for long-term survival of the regenerated tissue post-scaffold degradation. Lastly, the WA 18.4° was translated to a tubular graft and was shown to mirror the mechanical behaviour of small diameter vessels within physiological strain. Taken together, this study demonstrates the capacity to use MEW to fabricate bioinspired scaffolds to mimic the tunica media of vessels and recapitulate vascular mechanics which could act as a framework for small diameter graft development to guide tissue regeneration and orientation.

Hs27 fibroblast response to contact guidance cues

Contact guidance is the phenomena of how cells respond to the topography of their external environment. The morphological and dynamic cell responses are strongly influenced by topographic features such as lateral and vertical dimensions, namely, ridge and groove widths and groove depth (Rw,Gw,andGD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{R}}}_{{\ ext{w}}}, {{\ ext{G}}}_{{\ ext{w}}},\\,\\mathrm{and}\\,\\,{{\ ext{G}}}_{{\ ext{D}}}$$\\end{document}, respectively). However, experimental studies that independently quantify the effect of the individual dimensions as well as their coupling on cellular function are still limited. In this work, we perform extensive parametric studies in the dimensional space—well beyond the previously studied range in the literature—to explore topographical effects on morphology and migration of Hs27 fibroblasts via static and dynamic analyses of live cell images. Our static analysis reveals that the GD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{G}}}_{{\ ext{D}}}$$\\end{document} is most significant, followed by the Rw\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{R}}}_{{\ ext{w}}}$$\\end{document}. The fibroblasts appear to be more elongated and aligned in the groove direction as the GD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{G}}}_{{\ ext{D}}}$$\\end{document} increases, but their trend changes after 725 nm. Interestingly, the cell shape and alignment show a very strong correlation regardless of GD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{G}}}_{{\ ext{D}}}$$\\end{document}. Our dynamic analysis confirms that directional cell migration is also strongly influenced by the GD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{G}}}_{{\ ext{D}}}$$\\end{document}, while the effect of the Rw\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{R}}}_{{\ ext{w}}}$$\\end{document} and Gw\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{G}}}_{{\ ext{w}}}$$\\end{document} is statistically insignificant. Directional cell migration, as observed in the static cell behavior, shows the statistically significant transition when the GD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\ ext{G}}}_{{\ ext{D}}}$$\\end{document} is 725 nm, showing the intimate links between cell morphology and migration. We propose possible scenarios to offer mechanistic explanations of the observed cell behavior.

Technical note: Excel spreadsheet calculation of the Henssge equation as an aid to estimating postmortem interval

In forensic cases for which the time of death is unknown, several methods are used to estimate the postmortem interval. The quotient (Q) defined as the difference between the rectal and ambient temperature (Tr − Ta) divided by the initial difference (T0 − Ta) represents the progress of postmortem cooling: Q = (Tr − Ta)/(T0 − Ta), (1 ≥ Q ≥ 0). Henssge was able to show that with the body weight and its empirical corrective factor, Q can be reasonably predicted as a double exponential decay function of time (Qp(t)). On the other hand, actual Q is determined as Qd by measuring Tr and Ta under an assumption of T0 = 37.2 °C. Then, the t value at which Qp(t) is equal to Qd (Qd=Qp(t)) would be a good estimate of the postmortem interval (the Henssge equation). Since the equation cannot be solved analytically, it has been solved using a pair of nomograms devised by Henssge. With greater access to computers and spreadsheet software, computational methods based on the input of actual parameters of the case can be more easily utilized. In this technical note, we describe two types of Excel spreadsheets to solve the equation numerically. In one type, a fairly accurate solution was obtained by iteration using an add-in program Solver. In the other type (forward calculation), a series of Qp(t) was generated at a time interval of 0.05 h and the t value at which Qp(t) was nearest to Qd was selected as an approximate solution using a built-in function, XLOOKUP. Alternatively, a series of absolute values of the difference between Qd and Qp(t) (|Dq(t)| = |Qd − Qp(t)|) was generated with time interval 0.1 h and the t value that produces the minimum |Dq(t)| was selected. These Excel spreadsheets are available as Supplementary Files.

OPTIMAL CROPPING SEQUENCE OF SMALL-SCALE FARMS IN THE RAIN-FED SECTOR OF GADARIF STATE- SUDAN(1)

The study aimed to examine the Optimal Cropping Sequence of the main crops grown under the rain-fed sector of Gadarif state - Sudan: such as sorghum, millet, sesame and groundnuts. The study used both primary and secondary data. Multistage random sampling technique was used to collect primary data on small-scale farms from three villages of the state by means of questionnaire as a sample farmer from 175 of Gadarif State, during 2017 -2018 season. Secondary data were collected from Central Bureau of Statistics and Federal Ministry of Agriculture. Linear programming technique was used to determine the optimal cropping sequence of small-scale farms (less than 210ha) in the rain-fed sector of Gadarif state. Spread sheet of the excel solver was used to run the analysis. The results revealed that the current cultural practices and crop sequence, in which sorghum do not come after sesame, was not the optimal one. Food-crops (sorghum and millet) did not enter the optimal cropping pattern under the current sequences and policy measures, with sesame dominated the total land. The crop sequence of groundnuts, sesame, sorghum and millet proved to be the optimal cropping pattern that improves farmer’s returns. Under such sequence, the four crops entered the optimum plan and farmers’ returns exceed of the current situation by 181.94%, but if this sequence is used with the recommended full package of technological improvement, then farmers’ net returns will increase three times than the current practices. Small-scale farmers should be encouraged to adopt the crop sequence in which sorghum come after sesame. They should also be encouraged to change their mind to become commercially oriented (by following the crop sequences with greatest returns according to local and international demand and expected prices. Even if the subsistence crop is excluded).

Strategies for engineering neural cell alignment and their biomedical applications

Strategies for engineering neural cell alignment and their biomedical applications

Analysis of Projected Temperature Changes in Aceh Province

The objective is to analyse temperature changes and their future projection in Aceh. The activities consist of collecting past and future temperature data, preparing materials for processing, and analyzing past and future temperature data (climate change projections). The data used are monthly average temperature data from data global climate model, e.g., csiromk3.6-hist-1986-2005-tas, csiromk3.6-rcp45- 2016-2035-tas, csiromk3.6-rcp45-2046-2065-tas, csiromk3.6-rcp45-2081-2100- tas, csiromk3.6-rcp85-2016-2035-tas, csiromk3.6-rcp85-2046-2065-tas, and csiromk3.6-rcp85-2081-2100-tas. The study began with reading climate data in NetCDF format using GRADS software, data processing using CDO software, providing a coordinate system using QGIS software, making climate change projection maps using ArcGIS software, and making climate change graphs using spreadsheet programs. Two scenarios, i.e., RCP4.5 and RCP8.5 are used to analyse the projected temperature changes in the short-term (2016 – 2035), medium-term (2046-2065), and long-term (2081-2100). The results show that the RCP4.5 projection shows a lower change in temperature rise than the RCP 8.5. A change in a temperature rise of up to 5°C was found in the RCP8.5 scenario.

Evaluation of the impact of a Pharmacy Technician within the Emergency Department, Royal Stoke University Hospital

Abstract Introduction The Emergency Department (ED) at the Royal Stoke University Hospital has come under increasing pressure, and it is well published that patients within the ED are at a higher risk of medication misadventure and missed doses of critical medicines1. This was a particular risk at the Royal Stoke in winter 2022/23 with the re-introduction of ED corridor care and patients waiting over 24 hours for a medical bed. A prescribing pharmacist has been in post in the ED since 2019, but additional funding was obtained for a pharmacy ED technician to support for 6 months during winter pressures. Aim The aim of this service evaluation was to assess the impact of the pharmacy technician within the ED, with a particular focus on medicines reconciliation, allergy status recognition and pharmacist prescribing activity. Methods Ethical approval was not required for this project, as it was a service evaluation. Data was collected over an 11 week period, Monday-Friday from October-December 2022. Data was collated into an Excel® spread sheet and assessed the number of patients reviewed by the pharmacy technician and prescribing pharmacist, the number of medicines prescribed by a prescribing pharmacist (including number of critical and non-critical medicines), and any missed allergy status’ by the clerking practitioner. Results Over 11 weeks, the pharmacist prescriber was able to prescribe 183 medicines, 46 of which were critical medicines. 23 patients were identified as having allergies (with 61% being penicillin allergy) which had previously not been documented by the clerking practitioner within the ED and/or patients were not wearing the appropriate red allergy wristband. This included 2 patients who had previously experienced anaphylaxis as a result of their drug allergy. Finally, comparing the data from the time period with the pharmacy technician, to without a pharmacy technician, demonstrated an almost 10-fold increase in pharmacist prescribing activity. Discussion/Conclusion This service evaluation has demonstrated the significant positive impact of a pharmacy technician within the ED. The data collected for this service evaluation was limited as it was only collected on weekdays, and further work should be done to assess the impact of a 7 day service. It is therefore recommended that permanent funding is secured all year round for ED pharmacy technician support, ideally 7 days per week. This will increase medicines reconciliation activity allowing ED pharmacists to focus on clinical review and prescribing for patients, increasing the number of patients seen by pharmacy, allowing earlier identification of patients on critical medicines, reducing the number of missed doses and potential harm. A pharmacy technician also allows earlier confirmation of patients’ allergy status, further reducing harm within the ED.

A Study on Workload of a Medical Linear Accelerator at a High Throughput Cancer Treatment Centre in Sri Lanka

Radiotherapy bunker design depends on several factors, and among them, workload is one of the important factors. Workload is calculated from the radiation dose delivered at the isocenter. Due to the introduction of new radiotherapy treatment modalities and an increasing number of new cancer patients, there is a higher possibility to increase the workload. Therefore, this study aims to assess the workload of Varian linear accelerator vault at Apeksha Hospital, Maharagama. Data were collected from 1st of August 2020 to 30th November 2020. Dose delivered at isocenter from the 3D-CRT procedures with 6 MV and 15 MV photon energy, the IMRT procedures with 6 MV photon energy and the quality assurance (QA) procedures were collected from ARIA patient management system and transferred into Excel spread sheet for data analysis. The calculated weekly workload was 2326 Gy/week with a 43% contribution from the IMRT procedures with 6 MV, 39% contribution from the 3D-CDT procedures with 6 MV, 16% contribution from the 3D-CDT procedures with 15 MV and 2% contribution from physics workload (QA procedures). The evaluated workload is higher than the NCRP recommended workload of 1000 Gy/week. This study recommends for at least a one-year survey for more accuracy on workload assessment, and also to evaluate the use factor since most of the advanced radiotherapy treatment techniques use high number of monitor units which will increase the leakage radiation.

Tailoring the pore design of embroidered structures by melt electrowriting to enhance the cell alignment in scaffold-based tendon reconstruction

Tissue engineering of ligaments and tendons aims to reproduce the complex and hierarchical tissue structure while meeting the biomechanical and biological requirements. For the first time, the additive manufacturing methods of embroidery technology and melt electrowriting (MEW) were combined to mimic these properties closely. The mechanical benefits of embroidered structures were paired with a superficial micro-scale structure to provide a guide pattern for directional cell growth. An evaluation of several previously reported MEW fiber architectures was performed. The designs with the highest cell orientation of primary dermal fibroblasts were then applied to embroidery structures and subsequently evaluated using human adipose-derived stem cells (AT-MSC). The addition of MEW fibers resulted in the formation of a mechanically robust layer on the embroidered scaffolds, leading to composite structures with mechanical properties comparable to those of the anterior cruciate ligament. Furthermore, the combination of embroidered and MEW structures supports a higher cell orientation of AT-MSC compared to embroidered structures alone. Collagen coating further promoted cell attachment. Thus, these investigations provide a sound basis for the fabrication of heterogeneous and hierarchical synthetic tendon and ligament substitutes.

Digital Skills of Management Accountants: A Comparative Analysis across EU Countries

The Fourth Industrial Revolution is bringing significant changes to the digital skill set required of management accountants. Thus, to continue ensuring the profession's relevance, academia and professional bodies constantly seek to update their curricula to meet the business environment's necessities. Thus, the present research aims to identify the digital skills management accounting practitioners need by examining the companies' requirements and determining whether there are significant differences between European Union (EU) member states regarding the countries' digital performance. This study adopts a mixed-methods approach by combining qualitative and quantitative research methods to achieve this objective. The results obtained from the undertaken analyses reveal that most companies consider necessary basic digital skills, such as the effective use of spreadsheet software and competencies related to integrated systems, Business Intelligence, database management systems, and data warehouse management systems. In addition, the comparative review reveals that in countries with a high level of digital performance there is a significant impact on the professional requirements, with no differences being identified between countries with a medium and low level of digital performance, emphasising the changing role of practitioners as a result of the extensive management accounting processes' digitalisation. The research findings consequently have a series of implications for academia,professional bodies, and companies.

Microfluidic generation of bioinspired core–shell structured microfibers for cultured meat

The simulation of traditional meat characteristics is critical to cultured meat production. We propose bioinspired microfibers with solidified alginate shells and porcine muscle stem cell (PMSC) loaded hydrogel cores. The core–shell structure not only provide a spatially confined environment for directional cell alignment, but also enable the design of a soft hydrogel core to facilitate cell migration and mutual fusion. The myogenic differentiation and muscle protein synthesis of PMSCs in microfibers are thus significantly promoted, which even lead to the spontaneous contraction of cellular microfibers. Microfibers are assembled into bulk cultured meat tissues by integrating the microfluidics and 3D printing technologies. Benefiting from the efficient cell myogenesis, the appearance, texture, and protein composition of the constructed cultured meat are similar to those of native pork. By combining multiple microfluidic devices into the printing system, the simultaneous printing of multiple pieces of cultured meat can be realized as well. These features show the broad prospect of the proposed microfibers in efficient and large-scale production of cultured meat with traditional meat characteristics.

Fabrication and Characterisation of Hydrogels with Reversible Wrinkled Surfaces for Limbal Study and Reconstruction.

In the biomedical field, there is a demand for the development of novel approaches for the investigation of optical epithelial anatomical features with biomimetic materials. These materials are not only required to replicate structures but also enable dynamic modelling for disease states such as limbal stem cell deficiency and ageing. In the present study, the effective generation of reversible wrinkled polydimethylsiloxane (PDMS) substrates was undertaken to mimic the undulating anatomy of the limbal epithelial stem cell niche. This undulating surface pattern was formed through a dual treatment with acid oxidation and plasma using an innovatively designed stretching frame. This system enabled the PDMS substrate to undergo deformation and relaxation, creating a reversible and tuneable wrinkle pattern with cell culture applications. The crypt-like pattern exhibited a width of 70-130 µm and a depth of 17-40 µm, resembling the topography of a limbal epithelial stem cell niche, which is characterised by an undulating anatomy. The cytocompatibility of the patterned substrate was markedly improved using a gelatin methacrylate polymer (GelMa) coating. It was also observed that these wrinkled PDMS surfaces were able to dictate cell growth patterns, showing alignment in motile cells and colony segregation in colony-forming cells when using human and porcine limbal cells, respectively.

Short-Stranded Zein Fibers for Muscle Tissue Engineering in Alginate-Based Composite Hydrogels.

Cultivated meat is a nascent technology that aims to create an environmentally and animal-friendly alternative to conventional meat. Producing skeletal muscle tissue in an animal-free system allowing for high levels of myofusion and maturation is important for the nutritional and sensorial value of cultivated meat. Alginate is an attractive biomaterial to support muscle formation as it is food-safe, sustainable and cheap and can be crosslinked using non-toxic methods. Although alginate can be functionalized to promote cell attachment, limitations in its mechanical properties, including form, viscosity, and stress relaxation, hinder the cellular capacity for myogenic differentiation and maturation in alginate-based hydrogels. Here, we show that the addition of electrospun short-stranded zein fibers increased hydrogel degradation, resulting in faster compaction, improved cell-gel interaction, and enhanced alignment of bovine muscle precursor cells. We conclude that fiber-hydrogel composites are a promising approach to support optimal formation of 3D constructs, by improving tissue stability and thus prolonging culture duration. Together, this improves muscle-related protein content by facilitating myogenic differentiation and priming muscle organoids for maturation.

Fiber alignment in 3D collagen networks as a biophysical marker for cell contractility

Cells cultured in 3D fibrous biopolymer matrices exert traction forces on their environment that induce deformations and remodeling of the fiber network. By measuring these deformations, the traction forces can be reconstructed if the mechanical properties of the matrix and the force-free matrix configuration are known. These requirements limit the applicability of traction force reconstruction in practice. In this study, we test whether force-induced matrix remodeling can instead be used as a proxy for cellular traction forces. We measure the traction forces of hepatic stellate cells and different glioblastoma cell lines and quantify matrix remodeling by measuring the fiber orientation and fiber density around these cells. In agreement with simulated fiber networks, we demonstrate that changes in local fiber orientation and density are directly related to cell forces. By resolving Rho-kinase (ROCK) inhibitor-induced changes of traction forces, fiber alignment, and fiber density in hepatic stellate cells, we show that the method is suitable for drug screening assays. We conclude that differences in local fiber orientation and density, which are easily measurable, can be used as a qualitative proxy for changes in traction forces. The method is available as an open-source Python package with a graphical user interface.

Influence of nanosecond laser surface patterning on dental 3Y-TZP: Effects on the topography, hydrothermal degradation and cell response

ObjectivesLaser surface micropatterning of dental-grade zirconia (3Y-TZP) was explored with the objective of providing defined linear patterns capable of guiding bone-cell response. MethodsA nanosecond (ns-) laser was employed to fabricate microgrooves on the surface of 3Y-TZP discs, yielding three different groove periodicities (i.e., 30, 50 and 100 µm). The resulting topography and surface damage were characterized by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). X-Ray diffraction (XRD) and Raman spectroscopy techniques were employed to assess the hydrothermal degradation resistance of the modified topographies. Preliminary biological studies were conducted to evaluate adhesion (6 h) of human mesenchymal stem cells (hMSC) to the patterns in terms of cell number and morphology. Finally, Staphylococcus aureus adhesion (4 h) to the microgrooves was investigated. ResultsThe surface analysis showed grooves of approximately 1.8 µm height that exhibited surface damage in the form of pile-up at the edge of the microgrooves, microcracks and cavities. Accelerated aging tests revealed a slight decrease of the hydrothermal degradation resistance after laser patterning, and the Raman mapping showed the presence of monoclinic phase heterogeneously distributed along the patterned surfaces. An increase of the hMSC area was identified on all the microgrooved surfaces, although only the 50 µm periodicity, which is closer to the cell size, significantly favored cell elongation and alignment along the grooves. A decrease in Staphylococcus aureus adhesion was observed on the investigated micropatterns. SignificanceThe study suggests that linear microgrooves of 50 µm periodicity may help in promoting hMSC adhesion and alignment, while reducing bacterial cell attachment.